Managing hyperlypidaemia caused by protease inhibitors (PIs) with pravastatin (Lipostat) or bezafibrate (Bezalip) is significantly more effective than changing treatment to a non-nucleoside reverse transcriptase inhibitor (NNRTI), according to an Italian study published in the July 1st edition of AIDS. The investigators also found comparable immune and virological outcomes between patients taking lipid lowering drugs and those switching to an NNRTI. In addition they established that individuals taking pravastatin or bezafibrate were no more likely than those changing their highly active antiretroviral treatment (HAART) regimen to experience side-effects.
Investigators wished to compare the efficacy and safety of substituting nevirapine (Viramune) or efavirenz (Sustiva) for a protease inhibitor with the efficacy and safety of adding pravastatin or bezafibrate to a protease inhibitor-containing HAART regimen in patients with elevated triglycerides and cholesterol.
“This is the first randomised, open label, clinical trial…comparing protease inhibitor-sparing simplified therapy with hypolipidaemic pharmacological treatment for the management of HAART-induced dyslipidaemia,” comment the investigators from the St Orsola Hospital in Bologna and the University of Bologna.
To be eligible for the study patients had to be taking their first HAART regimen (consisting of two NRTIs and a protease inhibitor), be naïve to NNRTIs, and to have had a CD4 cell count above 350 cells/mm3, and a viral load below 50 copies/ml for at least six months. In addition, they were required to have had triglycerides above 200mg/dl, and total cholesterol above 250mg/dl, for at least six months' duration and for these elevated lipid levels to be unresponsive to changes in diet or exercise.
A total of 130 individuals met the recruitment criteria and enrolled in the study between 2001 and 2002. They were randomised into one of four arms in an open-label study lasting twelve months.
Patients in arm A switched their protease inhibitor for the NNRTI nevirapine. Those randomised to arm B stopped taking a protease inhibitor and initiated therapy with efavirenz. Individuals in arm C continued taking their current protease inhibitor-containing HAART regimen and started taking 20mg of pravastatin a day. Similarly, patients in arm D continued taking a protease inhibitor and were prescribed 400mg of bezafibrate daily.
There were no significant differences between the four arms of the study at baseline with regards to age, gender, mode of HIV infection, HIV disease stage, mean CD4 cell count, type and mean duration of anti-HIV therapy, and mean triglycerides and total cholesterol.
After twelve months, the mean reduction in triglyceride levels from baseline was 25% for patients who switched to nevirapine, 9% for patients switching to efavirenz, 41% for patients adding pravastatin and 47% for individuals who initiated treatment with bezafibrate. Patients switching to nevirapine had a statistically significant greater decline in their triglycerides than those switching to efavirenz (p
Similar results were observed for total cholesterol. Mean levels fell by 27% for patients switching to nevirapine, 10% for those switching to efavirenz, 46% for individuals taking pravastatin and 38% for patients taking bezafibrate.
A total of 19% of patients switching to an NNRTI achieved normal triglyceride levels compared to 51% of individuals taking lipid-lowering drugs (p
CD4 cell count and viral load were comparable across all four arms of the study, and all the treatment arms had a similar and favourable tolerability profile.
“In our study, pharmacological therapy with pravastatin or bezafibrate proved significantly more effective in the management of diet-resistant mixed hyperlipidaemia in HAART-treated patients than the switch from protease inhibitors to NNRTIs,” write the investigators.
Calza L et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 19 (10): 1051 – 1058, 2005.